AIMS/HYPOTHESIS: One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulin-resistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabetic patients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance. METHODS: Urinary proteins from timed overnight urine collections from 128 offspring of type 2 diabetic patients and 9 control subjects were analysed by western blotting using an antibody against nephrin. Glucose metabolism was assessed by OGTT and IVGTT and the euglycaemic-hyperinsulinaemic clamp technique. RESULTS: Of the offspring, 12.5% were strongly and 14.1% weakly positive for a 100-kDa urinary protein. All controls were negative. During the first 10 min of an IVGTT, the offspring strongly positive for the urinary protein had a higher insulin response than the offspring without the protein (3,700 vs 2,306 pmol l(-1)min(-1), p=0.007). Insulin sensitivity (the rate of whole-body glucose uptake divided by the steady-state insulin level x 100) was lower among the offspring strongly positive for the urinary protein than among the offspring negative for the protein (11.3 vs 15.8 micromol kg(-1)min(-1)pmol(-1)l(-1), p=0.008). CONCLUSIONS/ INTERPRETATION: A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabetic patients.
AIMS/HYPOTHESIS: One-third of normoalbuminuric type 1 diabeticpatients show immunoreactive nephrin in urine. Offspring of type 2 diabeticpatients are insulin-resistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabeticpatients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance. METHODS: Urinary proteins from timed overnight urine collections from 128 offspring of type 2 diabeticpatients and 9 control subjects were analysed by western blotting using an antibody against nephrin. Glucose metabolism was assessed by OGTT and IVGTT and the euglycaemic-hyperinsulinaemic clamp technique. RESULTS: Of the offspring, 12.5% were strongly and 14.1% weakly positive for a 100-kDa urinary protein. All controls were negative. During the first 10 min of an IVGTT, the offspring strongly positive for the urinary protein had a higher insulin response than the offspring without the protein (3,700 vs 2,306 pmol l(-1)min(-1), p=0.007). Insulin sensitivity (the rate of whole-body glucose uptake divided by the steady-state insulin level x 100) was lower among the offspring strongly positive for the urinary protein than among the offspring negative for the protein (11.3 vs 15.8 micromol kg(-1)min(-1)pmol(-1)l(-1), p=0.008). CONCLUSIONS/ INTERPRETATION: A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabeticpatients.
Authors: Robyn G Langham; Darren J Kelly; Alison J Cox; Renae M Gow; Harry Holthofer; Richard E Gilbert Journal: Nephrol Dial Transplant Date: 2004-01 Impact factor: 5.992
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Authors: R Nosadini; M R Cipollina; A Solini; M Sambataro; A Morocutti; A Doria; P Fioretto; E Brocco; B Muollo; F Frigato Journal: J Am Soc Nephrol Date: 1992-10 Impact factor: 10.121
Authors: M Kestilä; U Lenkkeri; M Männikkö; J Lamerdin; P McCready; H Putaala; V Ruotsalainen; T Morita; M Nissinen; R Herva; C E Kashtan; L Peltonen; C Holmberg; A Olsen; K Tryggvason Journal: Mol Cell Date: 1998-03 Impact factor: 17.970